Neuroepithelial stem cells (NESCs) are stem cells that retain the potential to differentiate into neurons or astrocytes. Although progress has been made in elucidating the regulatory pathways involved in neurogliogenesis, the molecular mechanisms that mediate these functions remain incompletely defined.
Lens epithelium-derived growth factor (LEDGF/p75) (see Singh et al., Invest Ophthalmol Vis Sci 40:1444-51 (1999); and Ge et al., Embo J. 17:6723-29 (1998)) is a transcriptional co-activator that belongs to the hepatoma-derived growth factor (HDGF) superfamily, whose member proteins include auto/paracrine growth factors and survival factors that possess bipartite nuclear localization signals. (See Singh et al., Biochem Biophys Res Commun 267:373-81 (2000)). For example, the HDGF superfamily includes HDGF and HDGF-related proteins. (See Dietz et al., Biochem J 366:491-500 (2002)).
LEDGF/p75 is highly expressed in the lens epithelium (see Singh et al., Biochem Biophys Res Commun 267:373-81 (2000)), which functions as a progenitor cell reservoir on the anterior surface of the crystalline lens. Lens epithelial cells transdifferentiate throughout life to generate long-lived post-mitotic lens fiber cells. A marked decrease in lens epithelial cell LEDGF/p75 expression has been shown to be tightly correlated with initiation of lens epithelial cell to fiber cell terminal differentiation. (See Kubo et al., Histochem Cell Biol 119:289-99 (2003)).